Division of Molecular Biology of the Cell II, German Cancer Research Center, DKFZ-ZMBH Alliance, 69120 Heidelberg, Germany.
Adolf Butenandt Institute and Center for Integrated Protein Science Munich, Ludwig-Maximilians-Universität, 80336 Munich, Germany.
Mol Cell. 2014 May 22;54(4):675-82. doi: 10.1016/j.molcel.2014.03.032. Epub 2014 Apr 24.
A complex network of regulatory pathways links transcription to cell growth and proliferation. Here we show that cellular quiescence alters chromatin structure by promoting trimethylation of histone H4 at lysine 20 (H4K20me3). In contrast to pericentric or telomeric regions, recruitment of the H4K20 methyltransferase Suv4-20h2 to rRNA genes and IAP elements requires neither trimethylation of H3K9 nor interaction with HP1 proteins but depends on long noncoding RNAs (lncRNAs) that interact with Suv4-20h2. Growth factor deprivation and terminal differentiation lead to upregulation of these lncRNAs, increase in H4K20me3, and chromatin compaction. The results uncover a lncRNA-mediated mechanism that guides Suv4-20h2 to specific genomic loci to establish a more compact chromatin structure in growth-arrested cells.
转录与细胞生长和增殖之间存在着复杂的调控途径网络。在这里，我们发现细胞静息通过促进组蛋白 H4 赖氨酸 20 位三甲基化（H4K20me3）来改变染色质结构。与着丝粒或端粒区域不同，H4K20 甲基转移酶 Suv4-20h2 募集到 rRNA 基因和 IAP 元件既不需要 H3K9 的三甲基化，也不需要与 HP1 蛋白相互作用，但需要与 Suv4-20h2 相互作用的长非编码 RNA（lncRNA）。生长因子剥夺和终末分化导致这些 lncRNA 的上调、H4K20me3 的增加和染色质紧缩。这些结果揭示了一种 lncRNA 介导的机制，该机制指导 Suv4-20h2 到特定的基因组位点，在生长停滞的细胞中建立更紧凑的染色质结构。
